DESCRIPTION ( Applicant's abstract): Triage Pharmaceuticals LLC ("Triage") was chartered in the summer of 1999 to exploit new treatments for vascular leakage related illnesses using NADPH oxidase inhibitors patented by Dr. James Holland, a Triage co-founder. The invention is protected by two issued U.S. patents, a granted European patent, and pending Japanese and Canadian patent applications. These cases claim a method of prevention and treatment of diseases related to endothelial hyper-permeability and vascular leakage by therapeutic administration of an NADPH oxidase inhibitor. The scientific rationale for the involvement of NADPH oxidase in mechanisms leading to vascular endothelial leakage has been well documented by Triage in its work on the inhibitory effect of apocynin, a naturally occurring plant extract, on the development of atheroscierosis. In order to further this work, Triage is seeking funding to perform accelerated pharmaceutical development and preclinical testing for drug candidates in a vascular leakage disease indication that has a clear, simple, non-costly end-point and treatment duration that should allow determination of clinical efficacy in very short trial periods. Using its current library of potent NADPH oxidase inhibitors, "proof of concept" will be established in the vascular leakage of diabetic retinopathy using the streptozotocin-treated diabetic rat model. PROPOSED COMMERCIAL APPLICATION: There are no currently available drugs for the treatment of the endothelial hyper-permeability and vascular leakage component of chronic vascular diseases, such as diabetes melitius, atherosclerosis and hypertension. Despite the effectiveness of currently available medical treatments for these vascular diseases, the risks of morbidity and mortality remain high. A combination approach with currently available medical treatment and an orally administered NADPH oxidase inhibitor would significantly improve the treatment of individuals with a high risk for the diseases.